Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1

• Type of Material: Article
• Authors: Katharina Fleischhauer, Essen University Hospital; Marcelo A. Fernandez-Vina, Stanford University; Tao Wang, Medical College of Wisconsin; Michael Haagenson, Center for International Blood and Marrow Transplant Research; Minoo Battiwalla, National Heart Lung and Blood Institute; Lee Ann Baxter-Lowe, University of California, San Francisco; Fabio Ciceri, San Raffaele Scientific Institute; Jason Dehn, National Marrow Donor Program; James Gajewski, Oregon Health and Science University; Gregory A. Hale, University of South Florida; Martin BA Heemskerk, Dutch Transplant Foundation; Susana R. Marino, University of Chicago Hospitals; Phillip L. McCarthy, Roswell Park Cancer Institute; David Miklos, Stanford Hospitals and Clinics; Machteld Oudshoorn, Leiden University; Marilyn S. Pollack, University of Texas Health Care System; Vijay Reddy, University of Florida; David Senitzer, City of Hope National Medical Center; Bronwen E. Shaw, Anthony Nolan Research Institute; Edmund K Waller, Emory University; Stephanie J. Lee, Fred Hutchinson Cancer Research Center; Stephen R. Spellman, Center for International Blood and Marrow Transplant Research
• Language: English
• Date: 2014-09-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Springer Nature Publishing AG
• Final Published Version (URL): http://dx.doi.org/10.1038/bmt.2014.122
• Title of Journal or Parent Work: Bone Marrow Transplantation
• ISSN: 0268-3369
• Volume: 49
• Issue: 9
• Start Page: 1176
• End Page: 1183
• Grant/Funding Information: This work was supported by a grant (no. IG12042) from the Associazione Italiana per la Ricerca sul Cancro (AIRC) to Katharina Fleischhauer.; Complete funding list available in full text.
• Keywords: SELECTION; Transplantation; VERSUS-HOST-DISEASE; Science & Technology; MARROW-TRANSPLANTATION; LEUKEMIA; Immunology; Hematology; MISMATCHES; LYMPHOCYTE INFUSION; Oncology; Biophysics; DONOR; Life Sciences & Biomedicine; DISPARITY; ALLELES; HLA-DP
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.